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Researchers have finally mapped the underlying whole-brain mechanisms for the use of DBS to alleviate symptoms of Parkinson's Disease.

Deep brain stimulation (DBS) for Parkinson’s disease (PD) has helped alleviate symptoms for over 150,000 patients but the underlying mechanisms have remained elusive. Now, thanks to the efforts of a large international team, led by PdD student Victor Saenger, Prof Morten Kringelbach and Prof Gustavo Deco from the Universities of Oxford (UK), Aarhus (Denmark) and Pompeu Fabra (Spain), researchers have finally mapped the underlying whole-brain mechanisms, published in the open-access journalScientific Reports.

The results of the study showed that DBS causes a global rebalancing of brain dynamics following, high frequency stimulation in the subthalamic nucleus in PD patients.

The researchers were able to record the brain activity of 10 patients with DBS ON and OFF in the MRI scanner. Using state-of-the-art computational modelling, the researchers were able to show the global effects that DBS has in rebalancing brain networks as well as to artificially apply DBS on a simulated brain. Furthermore, the research was also able to pinpoint the brain regions that change the most following stimulation.

Using our whole-brain computational model, we were able to identify a network of regions that significantly change when DBS is turned on while making the network activity closely similar to that found in healthy individuals.This is the first time that we have been able to study the widespread changes in human brain activity following DBS.- Victor Saenger

“Our findings help us understand why DBS is so effective in alleviating the symptoms of PD and may in time help identify new, perhaps even more effective brain targets,” said Victor Saenger.

Prof Kringelbach adds: “In general, the perspective of the present study is that we are now able to use whole-brain computational modelling to simulate the effects of brain interventions and predict the outcome. Longer term, we are hoping to be able to use these methods to personalize interventions for the benefit of individual patients. Still, it is important to carefully consider the risks and ethics of using something as invasive as deep brain stimulation.”

Parkinson’s disease (PD) is a devastating neurodegenerative disease that affects at least 10 million people worldwide. There is no known cure for PD but deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to help alleviate the symptoms in over 150,000 patients worldwide. This target for stimulation in the human brain was made possible by work back in 1989 by one of the co-authors Oxford neurosurgeon Prof Tipu Aziz, who together with Prof Alan Crossman of Manchester University discovered that lesioning the STN in non-human primates can alleviate Parkinsonism. Yet, despite the remarkable clinical efficacy of DBS, until the current study we did not fully understand the underlying mechanisms.

About whole-brain computational modelling

Technical advances mean that it is now possible to carefully model large-scale human brain activity recorded using brain scanning techniques such as functional magnetic resonance imaging. The advanced computational models utilises the underlying structure of the living human brain obtained through non-invasive neuroimaging and combine this with careful models of the neural activity and interactions between brain regions. Such models are becoming very good at predicting brain activity measured by neuroimaging. This opens up for the rational design of new therapeutic targets for deep brain stimulation.